The Globin Fragment LVV-Hemorphin-7 Is an Endogenous Ligand for the AT4 Receptor in the Brain

Abstract: Angiotensin IV (Val-Tyr-Ile-His-Pro-Phe) has been reported to interact with specific high-affinity receptors to increase memory retrieval, enhance dopamine-induced stereotypy behavior, and induce c- fos expression in several brain nuclei. We have isolated a decapeptide (Leu-Val-Val-Tyr-Pro-Trp-Thr-Gln-Arg-Phe) from sheep brain that binds with high affinity to the angiotensin IV receptor. The peptide was isolated using ¹²⁵I-angiotensin IV binding to bovine adrenal membranes to assay receptor binding activity. This peptide is identical to the amino acid sequence 30–39 of sheep β^A- and β^B-globins and has previously been named LVV-hemorphin-7. Pharmacological studies demonstrated that LVV-hemorphin-7 and angiotensin IV were equipotent in competing for ¹²⁵I-angiotensin IV binding to sheep cerebellar membranes and displayed full cross-displacement. Using in vitro receptor autoradiography, ¹²⁵I-LVV-hemorphin-7 binding to sheep brain sections was identical to ¹²⁵I-angiotensin IV binding in its pattern of distribution and binding specificity. This study reveals the presence of a globin fragment in the sheep brain that exhibits a high affinity for, and displays an identical receptor distribution with, the angiotensin IV receptor. This globin fragment, LVV-hemorphin-7, may therefore represent an endogenous ligand for the angiotensin IV receptor in the CNS.